Tralokinumab 150mg/1ml solution for injection pre-filled syringes

Atopic dermatitis (AD) is a chronic, inflammatory skin disease that can significantly affect quality of life. Presence, severity, and therapeutic response of AD are traditionally reported through clinical assessments including the Eczema Area and Severity Index or Investigator's Global Assessment. These clinical rating scales are visual assessments used in clinical trials to denotate AD severity. Alternatively, biomarkers open the potential to further enhance diagnosis of AD, assess disease status and severity, and potentially enable tailored treatment options for patients. Biomarkers can be classified according to their clinical use, clinical presentation, and underlying/endogenous molecular mechanisms. Specifically, interleukin (IL)-13, which has been shown to be a key biomarker in AD pathogenesis, can be used for prediction of AD development and to monitor clinical severity/response to treatment. Treatment with tralokinumab, a human monoclonal antibody that binds directly to-and subsequently blocks signaling of-IL-13, has been shown to reduce inflammation, re-balance the skin microbiome, and improve the skin barrier in patients with AD. In this review, key AD-related biomarkers, the role of IL-13 in driving AD pathogenesis, and the impact of IL-13 inhibition by tralokinumab on other AD-related biomarkers are discussed.

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Introduction: Atopic dermatitis (AD) and pruritic skin disorders are increasingly recognized in cancer patients. The management of these conditions in patients with a history or with concomitant cancer presents unique challenges, as traditional systemic therapies may pose risks due to their immunosuppressive effects. In recent years, biologic agents such as dupilumab and tralokinumab have emerged as promising treatments for AD, offering targeted modulation of the immune response with potentially fewer systemic side effects. This article aims to review the current evidence on the safety and efficacy of dupilumab and tralokinumab in treating AD and pruritus among cancer survivors, addressing the potential benefits and considerations for this unique patient population. Methods: A comprehensive analysis of the current medical literature was performed on the PubMed, Ovid, Scopus, Embase, and Cochrane Library databases until December 15, 2024. In conducting this narrative review, Medical Subject Headings (MeSH) terms and medical terminology related to clinical trials and real-life studies were employed, focusing on the pharmacological agents dupilumab, and tralokinumab. Discussion: Patients with active or past cancer are typically excluded from clinical trials of new medications, complicating the evaluation of cancer progression or recurrence risks in these patients setting. The potential use of biologic drugs like dupilumab and tralokinumab in oncological patients marks a significant breakthrough for treating conditions such as eczema and pruritus, which are common in this patient group. Although there are no explicit contraindications for using dupilumab and tralokinumab in patients with active cancer or a history of malignancy, there is no definitive guidance on their use in such cases. Real-world data is emerging, facilitated by collaboration between dermatologists and oncologists, supporting the effectiveness and safety of dupilumab and tralokinumab for managing AD in cancer patients. Nonetheless, larger studies with longer follow-up periods and dedicated pharmacovigilance programs are needed to substantiate these findings.

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Atopic dermatitis (AD) is a chronic inflammatory skin disorder that significantly affects patients' quality of life. Dupilumab, a monoclonal antibody targeting interleukin (IL)-4 receptor alpha (IL-4Rα), has been the standard biologic therapy for moderate-to-severe AD. This review compares dupilumab with tralokinumab-a promising alternative that selectively neutralizes IL-13-by examining their distinct mechanisms, clinical efficacy, safety profiles, and practical considerations. While both biologics are highly effective, pivotal monotherapy trials indicate numerically higher efficacy rates for dupilumab. Regarding safety, while long-term data show comparable rates of serious adverse events, dupilumab is associated with a higher incidence of both conjunctivitis and injection-site reactions. Key practical differences include dupilumab's broader indications and approval for infants (≥6 months), versus tralokinumab's flexible maintenance dosing and notable efficacy in head and neck AD. By highlighting these key distinctions, this review aims to support personalized treatment selection in AD. However, no direct head-to-head clinical trials have yet compared dupilumab and tralokinumab, and the available evidence is based on indirect comparisons from separate pivotal studies.

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BACKGROUND: Tralokinumab is a monoclonal antibody that specifically neutralizes interleukin (IL)-13, a key driver of skin inflammation and barrier abnormalities in atopic dermatitis (AD). This study evaluated early and 2-year impacts of IL-13 neutralization on skin and serum biomarkers following tralokinumab treatment in adults with moderate-to-severe AD. METHODS: Skin biopsies and blood samples were evaluated from a subset of patients enrolled in the Phase 3 ECZTRA 1 (NCT03131648) and the long-term extension ECZTEND (NCT03587805) trials. Gene expression was assessed by RNA sequencing; protein expression was assessed by immunohistochemistry and immunoassay. RESULTS: Tralokinumab improved the transcriptomic profile of lesional skin by Week 4. Mean improvements in the expression of genes dysregulated in AD were 39% at Week 16 and 85% at 2 years with tralokinumab, with 15% worsening at Week 16 with placebo. At Week 16, tralokinumab significantly decreased type 2 serum biomarkers (CCL17/TARC, periostin, and IgE), reduced epidermal thickness versus placebo, and increased loricrin coverage versus baseline. Two years of tralokinumab treatment significantly reduced expression of genes in the Th2 (IL4R, IL31, CCL17, and CCL26), Th1 (IFNG), and Th17/Th22 (IL22, S100A7, S100A8, and S100A9) pathways as well as increased expression of epidermal differentiation and barrier genes (CLDN1 and LOR). Tralokinumab also shifted atherosclerosis signaling pathway genes (SELE, IL-37, and S100A8) toward non-lesional expression. CONCLUSION: Tralokinumab treatment improved epidermal pathology, reduced systemic markers of type 2 inflammation, and shifted expression of key AD biomarkers in skin towards non-lesional levels, further highlighting the key role of IL-13 in the pathogenesis of AD. CLINICAL TRIAL REGISTRATION: NCT03131648, NCT03587805.

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Background: Tralokinumab, a humanized monoclonal antibody targeting interleukin-13, has been primarily used for the treatment of moderate-to-severe atopic dermatitis. Given its extensive use in clinical practice, understanding its safety profile in the real-world setting is crucial. Methods: This study utilized disproportionality analysis to evaluate the safety of tralokinumab in clinical practice by analyzing all adverse event reports since 2021 in the FDA Adverse Event Reporting System database that identified tralokinumab as the primary suspected drug. Reporting odds ratio, proportional reporting ratio, multi-item gamma Poisson shrinker, and Bayesian confidence propagation neural network were used for disproportionality analyses of adverse events related to tralokinumab. Additionally, the Weibull distribution was employed to model the risk of adverse events over time. Results: Adverse reactions documented on the drug label, such as injection site reactions, conjunctivitis, and upper respiratory infections, displayed positive signals. Additionally, potential adverse reactions not mentioned on the label were also identified, including dizziness, headache, nausea, vomiting, hair loss, and acne. The importance of adverse event monitoring, particularly in the first month after treatment initiation, was emphasized. Conclusion: This study has provided preliminary safety data on the real-world application of tralokinumab, confirming some known adverse reactions and revealing additional potential risks. The findings offer critical safety information for clinicians prescribing tralokinumab to treat atopic dermatitis.

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There is a need for long-term atopic dermatitis (AD) treatments that can effectively improve AD involvement of the head and neck (H&N) region (referred to as H&N AD). Tralokinumab, a high-affinity monoclonal antibody that neutralizes interleukin-13, is approved for the treatment of moderate-to-severe AD. Recent real-world studies have observed the effectiveness of tralokinumab for H&N AD. Here, data from phase III parent trials, ECZTRA 1 and ECZTRA 2, and the long-term extension trial, ECZTEND, were used to assess impacts of long-term tralokinumab treatment on H&N AD and the association between improvements in H&N AD and patient quality of life, and to evaluate whether a proportion of patients developed paradoxical H&N erythema. These post hoc analyses included data from all patients initiated on tralokinumab in ECZTRA 1 or ECZTRA 2. Patients were treated up to 4 years (i.e., up to 52 weeks in ECZTRA 1 or ECZTRA 2 plus up to 152 weeks in ECZTEND). Outcomes included body region subscores of the Eczema Area and Severity Index (EASI; H&N, upper limbs, trunk, lower limbs) and the Dermatology Life Quality Index (DLQI). Correlations between H&N EASI and DLQI were assessed with Spearman’s correlation coefficient (ρ). The incidence of paradoxical H&N erythema (defined as H&N EASI erythema increasing from baseline to a score of 3, while all other regional EASI subscores are 0 or 1, during two or more consecutive visits) was also assessed. Overall, 1192 patients who were initiated on tralokinumab in ECZTRA 1 and ECZTRA 2, of whom 523 patients opted to continue in ECZTEND, were analyzed. Percentages of patients who had H&N EASI ≤ 1 increased from 12.2% at parent trial baseline to 87.2% by week 152 of ECZTEND. Improvements in EASI subscore outcomes from parent trial baseline were comparable across body regions throughout all timepoints of the study. At parent trial week 16, H&N EASI was moderately correlated with total DLQI (ρ = 0.47), with the strongest numerical correlations observed for DLQI questions regarding skin discomfort (ρ = 0.43) and embarrassment due to skin (ρ = 0.40). During up to 4 years of treatment, seven tralokinumab-treated patients exhibited paradoxical H&N erythema, five of whom improved to absent or mild H&N EASI erythema with continued tralokinumab treatment. Tralokinumab provided progressive and sustained improvements in H&N AD, with H&N EASI 0/1 observed in nearly 90% of patients treated up to 4 years. Improvements in H&N EASI were similar to improvements observed for other body regions and were associated with improvements in patient quality of life, particularly for skin discomfort and self-consciousness/embarrassment due to skin. NCT03131648 (ECZTRA 1); study start date: 30 May, 2017; primary completion date: 7 August, 2018; study completion date: 10 October, 2019. NCT03160885 (ECZTRA 2); study start date: 12 June, 2017; primary completion date: 4 September, 2019; study completion date: 14 August, 2019. NCT03587805 (ECZTEND); study start date: 18 March, 2018; data cut-off date: 30 April, 2022; primary completion date: 3 July, 2024; study completion date: 3 July, 2024. Tralokinumab is an injectable treatment for atopic dermatitis capable of providing long-term disease control in the head and neck region. Atopic dermatitis (AD) is a chronic skin disease that can affect multiple body areas. Atopic dermatitis occurring in the head and neck region (referred to as H&N AD) can be especially burdensome owing in part to its high visibility. Additionally, H&N AD is challenging to treat and may show a lower clinical response to AD treatments than other body areas. Therefore, there is an increased demand for treatments that provide complete/almost complete skin clearance, especially around the face. Tralokinumab is an injectable medication approved for treating moderate-to-severe AD. It has been shown to improve H&N AD in real-world clinical settings. Here, data from phase III parent trials (ECZTRA 1 and ECZTRA 2) and the long-term extension trial (ECZTEND), funded by LEO Pharma A/S, were used to examine the impact of long-term tralokinumab treatment on H&N AD in adults with moderate-to-severe AD who were treated up to 4 years. We found that the severity of H&N AD, including facial redness (i.e., erythema), improved in patients treated with tralokinumab up to 4 years. These improvements in H&N AD were similar to improvements in other body regions and were associated with improvements in patient quality of life, particularly for skin discomfort and self-consciousness/embarrassment due to skin. Worsening or new facial redness has been sometimes observed with certain AD treatments. Very few tralokinumab-treated patients showed increased redness specific to the H&N region compared with other body sites. Most of these cases resolved with continued treatment. Overall, these findings show that tralokinumab effectively treats H&N AD.

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Tralokinumab is a monoclonal antibody selectively targeting IL-13, approved for moderate-to-severe atopic dermatitis (AD), for which real-world data are scarce. This prospective, observational, multicentric study aimed to assess the long-term effectiveness and safety of tralokinumab in patients with AD in a real-world setting. Primary outcomes included 50%, 75%, and 90% improvement in Eczema Area and Severity Index score (EASI50, EASI75, EASI90, respectively) and improvements in Dermatology Life Quality Index (DLQI) at 1 year. A total of 136 patients with AD were enrolled in the study; data at 1-year follow-up were available for 111 patients. After 1 year, 68.5% and 33.3% of patients achieved an EASI75 and EASI90, respectively. A significantly higher percentage of patients with than without foot involvement achieved EASI50 (p = 0.009) and EASI75 (p = 0.022). Similarly, hand involvement was significantly associated with higher EASI50 response (p = 0.005). Median DLQI score decreased from 9.00 (interquartile range (IQR): 6.00, 13.75) to 1.00 (IQR: 0.00, 4.00) after 1 year of treatment. Adverse events included blepharitis (n = 10), conjunctivitis (n = 6), and injection-site reactions (n = 2). Tralokinumab can be an effective and safe treatment for patients with moderate-to-severe AD. Involvement of certain body areas, such as hands and feet, might positively predict a clinical response to tralokinumab.

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